Pesticidal and parasiticidal pyrazole-isoxazoline compounds

Abstract

The present invention relates to pesticidal and parasiticidal isoxazoline of formula (I) and salts thereof: wherein variables R 1 , P, Y and Q are described herein are as defined in the description. The invention also relates to parasiticidal and pesticidal compositions comprising the isoxazoline compounds of formula (I), processes for their preparation and their uses to prevent or treat parasitic infections or infestations in animals and as pesticides.

What is claimed is: 
     
       1. A pesticidal isoxazoline compound of formula (I): 
       
         
           
           
               
               
           
         
         or a pharmaceutically or agriculturally acceptable salt thereof, wherein:
 the asterisk (*) signifies a quaternary center; 
 P is an optionally substituted pyrazole ring; 
 R 1  is alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, alkylcycloalkyl or cycloalkylalkyl, each optionally substituted with one or more substituents independently selected from R 6 ; 
 Y is an optionally substituted phenylene, naphthylene, indanylene, a 5- or 6-membered heteroarylene, an 8-12-membered heterobicyclylene or an 8-12-membered heterotricyclylene, each optionally independently substituted by one or more R 7 ; 
 Q is X—NR 5 R 6 , —NR 5 R 6 , X—R 6 , OH, NH 2 , alkoxy, haloalkoxy, alkylamino, haloalkylamino, dialkylamino, dihaloalkylamino, thiol, alkylthio, haloalkylthio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, —SF 5 , —C(═S)—NH 2 , or an optionally substituted 5- or 6-membered carbocyclyl, heterocyclyl, heteroaryl ring or the groups T1 or T2: 
 
       
       
         
           
           
               
               
           
         
         
           wherein W is O or S; 
           X is (CH 2 )n, CH(CH 3 ), CH(CN), C(═O) or C(═S); 
           R 5  is H, alkyl, alkenyl, alkynyl, cycloalkyl, alkylcycloalkyl, cycloalkylalkyl, alkylcarbonyl or alkoxycarbonyl; 
           R 6  is H, OR 10 , NR 11 , R 12  or Q 1 ; alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, alkylcycloalkyl, cycloalkylalkyl, alkylcarbonyl, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl or dialkylaminocarbonyl, each optionally substituted with one or more substituents independently selected from R 7 ; or 
           R 5  and R 6  taken together with the nitrogen to which they are attached to form a ring containing 2 to 6 atoms of carbon and optionally one additional atom selected from the group consisting of N, S and O, said ring optionally substituted with 1 to 4 substituents independently selected from the group consisting of alkyl, halogen, —CN, —NO 2  and alkoxy; 
           each R 7  is independently halogen; alkyl, cycloalkyl, alkoxy, alkylthio, haloalkylthio, alkylsulfinyl, haloalkylsulfinyl, alkyl sulfonyl, haloalkylsulfonyl, alkylamino, haloalkylamino, dialkylamino, dihaloalkylamino, cycloalkylamino, alkylcarbonyl, alkoxycarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, haloalkylcarbonyl, haloalkoxycarbonyl, haloalkylaminocarbonyl, dihaloalkylaminocarbonyl, hydroxy, —SF 5 , —C(═S)NH 2 , —NH 2 , —CN or —NO 2 ; or Q 2 ; 
           each R 8  is independently halogen, alkoxy, haloalkoxy, alkylthio, haloalkylthio, alkylsulfinyl, haloalkylsulfinyl, alkyl sulfonyl, haloalkylsulfonyl, alkylamino, dialkylamino, alkoxycarbonyl, —SF 5 , —C(═S)NH 2 , —CN or —NO 2 ; 
           each R 9  is independently halogen, alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkoxy, haloalkoxy, alkylthio, haloalkylthio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, alkylamino, dialkylamino, —SF 5 , —C(═S)NH 2 , —CN, —NO 2 , phenyl or pyridinyl; 
         
         R 10  is H; or alkyl, alkenyl, alkynyl, cycloalkyl, alkylcycloalkyl or cycloalkylalkyl, each optionally substituted with one of more halogen; 
         R 11  is H, alkyl, alkenyl, alkynyl, cycloalkyl, alkylcycloalkyl, cycloalkylalkyl, alkylcarbonyl or alkoxycarbonyl; 
         R 12  is H; Q 3 ; or alkyl, alkenyl, alkynyl, cycloalkyl, alkylcycloalkyl or cycloalkylalkyl, each optionally substituted with one or more substituents independently selected from R 7 ; or 
         R 11  and R 12  taken together with the nitrogen to which they are attached to form a ring containing 2 to 6 atoms of carbon and optionally one additional atom selected from the group consisting of N, S and O, said ring optionally substituted with 1 to 4 substituents independently selected from the group consisting of alkyl, halogen, —CN, —NO 2  and alkoxy; 
         Q 1  is a phenyl ring, a 5- or 6-membered heterocyclic ring, or an 8-, 9- or 10-membered fused bicyclic ring system optionally containing one to three heteroatoms selected from up to 1 O, up to 1 S and up to 3 N, each ring or ring system optionally substituted with one or more substituents independently selected from R 8 ;
 Q 2  is independently a phenyl ring or a 5- or 6-membered heterocyclic ring, each ring optionally substituted with one or more substituents independently selected from R 9 ; 
 Q 3  is a phenyl ring or a 5- or 6-membered heterocyclic ring, each ring optionally substituted with one or more substituents independently selected from R 9 ; and n is 0, 1 or 2. 
 
       
     
     
       2. The pesticidal isoxazoline compound of  claim 1 , wherein P is P 1 , P 2 , P 3  or P 4 : 
       
         
           
           
               
               
           
         
         wherein, R 2  and R 3  are independently H, halogen, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, halocycloalkyl, alkoxy, haloalkoxy, alkoxyalkyl, alkoxyalkoxyalkyl, alkylthio, haloalkylthio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, amino, alkylamino, dialkylamino, haloalkylamino, dihaloalkylamino, alkylcarbonyl, haloalkylcarbonyl, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl, SF 5 , —CN, —NO 2  or —C(S)NH 2 , wherein each alkyl, cycloalkyl, alkenyl, alkynyl, aryl or heteroaryl is optionally independently substituted by one or more R 7 ; 
         R 4  is H, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, arylalkyl, heteroarylalkyl, alkoxyalkyl, alkoxyalkoxyalkyl, alkylcarbonyl, haloalkylcarbonyl, alkoxycarbonyl, haloalkoxycarbonyl, alkylsulfinyl, haloalkylsulfinyl, alkyl sulfonyl, haloalkylsulfonyl, aryl, heteroaryl, arylalkyl or heteroarylalkyl, wherein each optionally substituted by one or more R 7 . 
       
     
     
       3. The pesticidal isoxazoline compound of  claim 1 , wherein Y is Y-1, Y-2, Y-3, Y-4, Y-5 or Y-6: 
       
         
           
           
               
               
           
         
         wherein Z 1 , Z 2 , Z 3 , Z 4 , Z 5  and Z 6  are independently N or C—R 15  and wherein at most 3 Z groups are nitrogen; 
         Z is N or C-R 15 ; and 
         R 13  and R 15  are independently H, halogen, C 1 -C 3 alkyl, C 1 -C 3 haloalkyl, C 1 -C 3 alkoxy, C 1 -C 3 haloalkoxy, C 1 -C 3 alkylthio, C 1 -C 3 haloalkylthio, C 1 -C 3 alkylsulfinyl, C 1 -C 3 haloalkylsulfinyl, C 1 -C 3 alkylsulfonyl, C 1 -C 3 haloalkylsulfonyl, —CN, —NO 2  or —SF 5 . 
       
     
     
       4. The pesticidal isoxazoline compound of  claim 1 , wherein R 1  is CF 3 . 
     
     
       5. The pesticidal isoxazoline compound of  claim 2 , wherein R 2  and R 3  are independently hydrogen, methyl or CF 3 ; and R 4  is hydrogen or C 1 -C 3 -alkyl. 
     
     
       6. The pesticidal isoxazoline compound of  claim 3  wherein:
 Y is Y-2, Y-3, Y-5 or Y-6; 
 Z 1 , Z 2 , Z 3 , Z 4 , Z 5  or Z 6  are independently N or C—H; 
 Z is N or C—H; and 
 each R 13  is H or C 1 -C 3 alkyl. 
 
     
     
       7. The pesticidal isoxazoline compound of  claim 1 , wherein Q is X—NR 5 R 6 . 
     
     
       8. The pesticidal isoxazoline compound of  claim 7 , wherein R 5  is H, C 1 -C 3 alkyl or C 1 -C 3 haloalkyl; and R 6  is C 3 -C 8 cycloalkyl, haloalkyl or alkyl optionally substituted by one or more R 7 . 
     
     
       9. The pesticidal isoxazoline compound of  claim 7 , wherein Q is —C(O)NHCF 3 , —C(O)NHCH 2 CH 2 CF 3 , —C(O)NHCH 2 CF 3 , —C(O)NHCH 2 C(O)NHCH 2 CF 3 , —C(O) NHCH 2 CH 2 S(O) n CH 3  where n is 0, 1 or 2 or —C(O)CH 2 S(O) n CH 3  where n is 0, 1 or 2. 
     
     
       10. The pesticidal isoxazoline compound of  claim 7 , wherein R 5  is H or C 1 -C 3 alkyl; and R 6  is cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl. 
     
     
       11. The pesticidal isoxazoline compound of  claim 1 , wherein Q is T1 or T2. 
     
     
       12. The pesticidal isoxazoline compound of  claim 1 , wherein the compound is selected from the group consisting of: 
       
         
           
                 
                 
               
                     
                 
                   Compound # 
                   Structure 
                 
                     
                 
                   2-1 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   2-2 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   2-3 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   2-4 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   2-5 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   2-6 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   2-7 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   2-8 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   2-9 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   2-10 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   2-11 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   2-12 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   2-13 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   2-14 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   2-15 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   2-16 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   2-17 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   2-18 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   2-19 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   2-20 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   2-21 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   2-22 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   2-23 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   2-24 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   2-25 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   2-26 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   2-27 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   2-28 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   2-29 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   2-30 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   2-31 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
             
                
                
                
               
               
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
       13. The pesticidal isoxazoline compound of  claim 1  wherein the isoxazoline compound is substantially enriched in the (S)-enantiomer. 
     
     
       14. A pesticidal composition comprising the isoxazoline compound of formula (I) of  claim 1 , or an agriculturally acceptable salt thereof, in combination with a agriculturally acceptable carrier. 
     
     
       15. A parasiticidal composition comprisingan isoxazoline compound of formula (I) of  claim 1 , or a pharmaceutically acceptable salt thereof, in combination with a pharmaceutically acceptable carrier.